Disorders of solute and water balance are a significant cause of morbidity and mortality in virtually all areas of medicine in every part of the world. Thus, a working knowledge of the physiology and pathophysiology of water and solute homeostasis is essential for every practicing physician. The principal elements in the control of solute and water balance in humans are well known. Some of them, such as the mechanisms that regulate the renal excretion of water and solute, have been studied extensively at the level of the cell as well as the whole body. However, much less is known about the regulation of other important variables such as intake or extrarenal output. There is even less reliable information about the way the various parts of the regulatory system interact to maintain water and solute balance in healthy people during normal activities or under the conditions in which patients are often studied and treated. Particularly lacking in this regard are reliable data concerning the scope and causes of normal variation between individuals as well as between different age, gender, ethnic or racial groups. It is clear, for example, that healthy young caucasian adults of both sexes show very large, genetically determined inter-individual differences in the osmoregulation of both thirst and secretion of the antidiuretic hormone, arginine vasopressin (1) but it is not known how these differences translate into individual variation in overall water and solute homeostasis. The best available information on normal variation in urine volume in adults (2) indicates a range from 600 to 1600 ml/24 hours but does not relate these values to gender, race, environmental conditions or variations in body size or solute load. Moreover, the validity of this normal range is highly dubious because a recent study of 12 healthy young adult volunteers in the CRC (3,4)revealed that 25% of them had urine outputs between 1800 and 3600 ml/24hours. Clearly, it is important to determine if this discrepency is due to faulty methodology in the earlier study, to hospitalization or selection bias in our own study or simply to cultural changes in eating and drinking habits in the last 50 years. Similar uncertainties pertain to the published normal values for urinary solute excretion, fluid intake and insensible water loss which must also vary markedly from person to person depending on genetic and environmental factors. Clarification of these issues is needed to provide a more rational foundation for differentiating disease from normal variation in individual patients.